The purpose of this research is to identify the cell surface molecules responsible for adhesion between both normal embryonic and malignant cells, and to determine the role played by differences in the intensities of intercellular adhesions in controlling cell rearrangement during embryonic development and in malignancy. Our approach has been as follows. We produce or obtain specific, multivalent, cell-surface-binding molecules. We modify these to a non-agglutinating form and find, among these, the molecules that inhibit cell adhesion. The target sites of these adhesion-inhibiting "site-blocker" molecules may well play a role in intercellular adhesion, possibly as direct cell ligands. We are pursuing evidence that a particular galNAc-containing surface antigen may mediate adhesions between several different chick embryonic tissues and between mouse 3T3 cells and possibly tumor cells as well. We are isolating and propose to identify these cell surface antigens and define their role in cell adhesion and morphogenesis. The intensities of intercellular adhesions can determine the movements and organization of both embryonic and malignant cells. Until now, most measurements of "cell adhesiveness" have reflected not the intensities but the rates of cell adhesion. We are developing a simple method for measuring the intercellular adhesive intensities of cells within aggregates. This should enable us and others to test existing theories relating the strengths of cell-cell adhesion to the determination of embryonic and malignant cell behavior.